title: Herpes simplex virus 1 ICP22 but not US 1.5 is required for efficient acute replication in mice and VICE domain formation.
abstract: The herpes simplex virus 1 (HSV-1) immediate-early protein, infected cell protein 22 (ICP22), is required for efficient replication in restrictive cells, for virus-induced chaperone-enriched (VICE) domain formation, and for normal expression of a subset of viral late proteins. Additionally, ICP22 is important for optimal acute viral replication in vivo. Previous studies have shown that the US1 gene that encodes ICP22, produces an in-frame, N-terminally truncated form of ICP22, known as US1.5. To date, studies conducted to characterize the functions of ICP22 have not separated its functions from those of US1.5. To determine the individual roles of ICP22 and US1.5, we made viral mutants that express either ICP22 with an M90A mutation in the US1.5 initiation codon (M90A) or US1.5 with three stop codons introduced upstream of the US1.5 start codon (3×stop). Our studies showed that, in contrast to M90A, 3×stop was unable to replicate efficiently in the eyes and trigeminal ganglia of mice during acute infection, to efficiently establish a latent infection, or to induce VICE domain formation and was only mildly reduced in its replication in restrictive HEL-299 cells and murine embryonic fibroblasts (MEFs). Both mutants enhanced the expression of the late viral proteins virion host shutoff (vhs) and glycoprotein C (gC) and inhibited viral gene expression mediated by HSV-1 infected cell protein 0 (ICP0). When we tested our mutants' sensitivity to type I interferon (beta interferon [IFN-β]) in restrictive cells, we noticed that the plating of the ICP22 null (d22) and 3×stop mutants was reduced by the addition of IFN-β. Overall, our data suggest that US1.5 partially complements the functions of ICP22.
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA.
authors.forename: Heba H
authors.initials: HH
authors.lastname: Mostafa
authors.forename: David J
authors.initials: DJ
authors.lastname: Davido
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D005260:Female; D006561:Herpes Simplex / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D014709:Vero Cells; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C057294:ICP22 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D018832:Molecular Chaperones; C586122:US1.5 protein, herpes simplex virus 1; D054334:Viral Regulatory and Accessory Proteins